{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:31:54Z","timestamp":1786516314975,"version":"build-2736575974"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101533"],"award-info":[{"award-number":["82101533"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873361"],"award-info":[{"award-number":["81873361"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870906"],"award-info":[{"award-number":["81870906"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    Alzheimer's disease (AD) presents a complex pathogenesis involving amyloid-\u03b2 (A\u03b2) plaques, tau tangles, and neuroinflammation. Recent evidence highlights \u03b4-opioid receptor (DOR) as a unique and promising therapeutic target for AD. This review summarizes current knowledge on DOR's multifaceted neuroprotective role in AD pathology. While its involvement in A\u03b2 regulation appears context-dependent, DOR activation consistently attenuates tau hyperphosphorylation, modulates microglial dysfunction, suppresses harmful neuroinflammation and inhibits complement-mediated synaptic pruning. All these findings have been well documented in\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    AD animal models. Furthermore, preclinical findings from general depression and anxiety models indicate that selective DOR agonists could help alleviate neuropsychiatric symptoms like depression and agitation, which are commonly seen in AD. DOR-associated genetic markers have also shown AD diagnostic potential. We conclude that targeting DOR offers a novel and integrative strategy impacting key AD pathological hallmarks: A\u03b2, tau, and neuroinflammation, as well as managing cognitive and emotional symptoms. Future research should focus on elucidating precise molecular mechanisms and translating these findings into clinical applications for AD diagnosis and therapy.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1891339","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:00:14Z","timestamp":1786514414000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The delta-opioid receptor: a therapeutic target for Alzheimer's disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Yuan","family":"Xu","sequence":"first","affiliation":[{"name":"Departments of Neurosurgery, The First People's Hospital of Changzhou","place":["Changzhou, Jiangsu, China"]},{"name":"Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University","place":["Changzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guan","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery, The First People's Hospital of Changzhou","place":["Changzhou, Jiangsu, China"]},{"name":"Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University","place":["Changzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery, The First People's Hospital of Changzhou","place":["Changzhou, Jiangsu, China"]},{"name":"Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University","place":["Changzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, The First People's Hospital of Changzhou","place":["Changzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xia","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University","place":["Shanghai, China"]},{"name":"Department of TCM, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Peng","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery, The First People's Hospital of Changzhou","place":["Changzhou, Jiangsu, China"]},{"name":"Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University","place":["Changzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"121803","DOI":"10.1016\/j.lfs.2023.121803","article-title":"Contribution of the opioid system to depression and to the therapeutic effects of classical antidepressants and ketamine","volume":"326","author":"Adzic","year":"2023","journal-title":"Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"933356","DOI":"10.3389\/fphar.2022.933356","article-title":"Development of a novel cell-based, in-cell Western\/ERK assay system for the high-throughput screening of agonists acting on the delta-opioid receptor","volume":"13","author":"Asghar","year":"2022","journal-title":"Front. 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